BOX (2022)
It is unknown whether we should be targeting higher blood pressures after ROSC. A higher MAP may offer advantages due to improved cerebral perfusion pressure, however data is lacking. The BOX trial examines both oxygen targets and BP targets in comatose survivors of OHCA. See also ACLS - Post-Cardiac Arrest Care.
Design Brief
Danish ICU x 2, double blind, parallel-group RCT. N=789 patients.
| Design | |
|---|---|
| Population | comatose adults with OHCA admitted to the hospital/ICU with GCS <= 0, at least 20 minutes of ROSC, and [[Targeted Temperature Management |
| Exclusion | conscious patients, pregnancy, non-cardiac OHCA, IHCA, bleeding diathesis, ICH, stroke, temperature on admission <30 C, persistent Cardiogenic Shock |
| Oxygen target | Restrictive (PaO2 68 to 75 mmHg, initial FiO2 0.3) vs liberal (98 to 105 mmHg, initial FiO2 0.6). Minimum target SpO2 >= 93%. |
| Blood pressure target | Lower MAP (63 mmHg) vs higher MAP (77 mmHg) |
| TTM | all patients had TTM at 36C with sedation and mechanical ventilation for at least 24 hours, after which normothermia and sedation weaning were targeted |
| Analysis | ITT analysis, prespecified subgroups, no data imputation, well-balanced baseline characteristics |
Outcomes
Primary Outcome
Good vs poor neurologic outcome: Composite of death from any cause or hospital discharge with severe disability or coma (CPC 3 or 4) within 90d after randomization (whichever occurred 1st).
| Arm | Restrictive | Liberal | Interpretation |
|---|---|---|---|
| O2 | 32% | 34% | HR 0.95, p=0.69 |
| BP | 32% | 34% | HR 1.08, p=0.56 |
Secondary Outcomes
Death at 90 days
| Arm | Restrictive | Liberal | Interpretation |
|---|---|---|---|
| O2 | 29% | 31% | HR 0.93 |
| BP | 29% | 31% | HR 1.13 |
Other
- No real differences in CPC, mRS, MoCA, adverse events.
- Separation of blood pressure values was achieved with a mean difference of 10.7mmhg (95% CI 10.0 to 11.4). The norepinephrine dose and vasopressor-inotropic score was higher in the high-target group.
Population
- Shockable rhythm: 85%
- Witnessed arrest: 85%
- Bystander CPR: 87%
- Time until ROSC: 21min
- Immediate coronary angiography: 91%
- PCI: 42%
Summary
- Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in similar incidence of death or severe disability or coma.
- Targeting a mean arterial blood pressure of 77mmHg or 63mmHg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma.
Personal Practice Takeaways
For patients who suffer decreased neurologic status post-OHCA: - Titrate FiO2 to maintain PaO2 68 to 105 mmHg - Maintain BP with MAP >= 63 to 65 mmHg
References
- Schmidt HJ et al. Oxygen Targets in Comatose Survivors of Cardiac Arrest. NEJM 2022. PMID: 360027567
- Kjaergaard J et al. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. NEJM 2022. PMID: 36027564
- Trial finds no benefit of raising blood pressure target in post cardiac arrest patients